Abstract: TH-PO1266
Cross-Ancestry Transferability of a Tubulointerstitial Molecular Classification to an Indigenous West African Cohort with Proteinuric Disease
Session Information
- Late-Breaking Research Posters
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Annor-Apaflo, Maame Esi Boikie, University of Ghana, Accra, Greater Accra Region, Ghana
- Eichinger, Felix H., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
- Halasz, Gabor, Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
- Nair, Viji, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
- Alaba, Mathew Olakunle, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
- Ni, Min, Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
- Godfrey, Brad A., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
- Sharif-Rodriguez, Wanda, Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
- Haas, Mary E., Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
- Morton, Lori, Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
- Devalaraja-Narashimha, Kishor B., Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
- Hodgin, Jeffrey B., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
- Kretzler, Matthias, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
- Adu, Dwomoa, University of Ghana, Accra, Greater Accra Region, Ghana
- Ojo, Akinlolu, The University of Kansas School of Medicine, Kansas City, Kansas, United States
Background
As nephrology advances precision medicine through multi-omics, African populations remain underrepresented in these efforts. We present transcriptomic subtyping of proteinuric disease in an indigenous West African cohort and evaluate cross-population transferability of molecular phenotypes using a kidney disease classification tool (Reznichenko et al., 2024).
Methods
Consensus clustering of tubulointerstitial (TI) transcriptomic profiles from 306 patients with proteinuric diseases in the H3Africa Kidney Disease Research Network cohort was followed by characterization using differential gene expression and pathway enrichment. Clusters were then mapped onto a 4-class self-organizing map (SOM)-based molecular classifier developed using primarily European TI transcriptomic profiles (Blue/Olive/Plum/Gold, kidneyclass.org) and evaluated against interstitial fibrosis/tubular atrophy (IFTA) scores.
Results
Three clusters were identified (T1=162, T2=59, T3=85). T1 had a metabolically active signature; T3 an immune-activated, fibrotic signature. T2, enriched for hemoglobin and mitochondrially encoded genes, was excluded pending resolution of biological vs. technical origin; T1/T3 assignments were robust to re-clustering (T1=160, T3=87). T1 & T3 mapped to the SOM classifier with strong concordance (Cramér's V=0.79, Figure 1A). T1 mapped predominantly to the least severe classes (Blue/Olive), T3 to the most severe (Plum/Gold). T3 had higher IFTA than T1 (median 10% vs 0%, p=1.35e-08). IFTA differed significantly across SOM classes (p=1.93e-10), with the gold class showing the highest median IFTA (Figure 1B).
Conclusion
This TI transcriptomic characterization of an indigenous West African cohort with proteinuric disease showed molecular clustering into distinct disease severity patterns that was aligned with the SOM molecular classifier, originally developed using a European dataset. Further analysis may help identify population-specific disease biology, underscoring the value of including African cohorts in precision nephrology.
Acknowledgment
H3Africa Kidney Disease Research Network
Funding
- Commercial Support – Regeneron Pharmaceuticals Inc.